Ultrasonographic imaging and anti-inflammatory therapy of muscle and tendon injuries using polymer nanoparticles

Ultrasonography is a reliable diagnostic modality for muscle and tendon injuries, but it has been challenging to find right diagnosis of minor musculoskeletal injuries by conventional ultrasonographic imaging. A large amount of hydrogen peroxide (H₂O₂) are known to be generated during tissue damages such as mechanical injury and therefore H₂O₂ holds great potential as a diagnostic and therapeutic marker for mechanical injuries in the musculoskeletal system. We previously developed poly(vanillyl alcohol-co-oxalate) (PVAX), which rapidly scavenges H₂O₂ and exerts antioxidant and anti-inflammatory activity in H₂O₂-associated diseases. Based on the notion that PVAX nanoparticles generate CO₂ bubbles through H₂O₂-triggered hydrolysis, we postulated that PVAX nanoparticles could serve as ultrasonographic contrast agents and therapeutic agents for musculoskeletal injuries associated with overproduction of H₂O₂. In the agarose gel phantom study, PVAX nanoparticles continuously generated CO₂ bubbles to enhance ultrasonographic echogenicity significantly. Contusion injury significantly elevated the level of H₂O₂ in skeletal muscles and Achilles tendons. Upon intramuscular injection, PVAX nanoparticles significantly elevated the ultrasound contrast and suppressed inflammation and apoptosis in the contusion injury of musculoskeletal systems. We anticipate that PVAX nanoparticles hold great translational potential as theranostic agents for musculoskeletal injuries.